[unreadable] This competitive renewal continues the goal of devising a computer-based virtual-endoscopic system for more effective lung-cancer assessment. It is driven by the following hypothesis: A synergistic combination of 3D MDCT imaging, image processing, and bronchoscopy improves current procedures for the staging, diagnosis, and treatment of lung cancer. The system devised to date known as the Virtual Navigator combines three-dimensional (3D) multidetector computed tomography (MDCT) imaging and bronchoscopy. It has shown great promise for 3D pulmonary CT image assessment and for image-guided bronchoscopic biopsy within the mediastinum. The objectives of this renewal are to build on these successes. In particular we now propose to develop and test methods that enable: (1) comprehensive nonsurgical staging of the mediastinal lymph nodes; (2) extension of our basic guidance system for the bronchoscopic biopsy of peripheral lung nodules; (3) positive characterization and selection of lung nodules needing biopsy. The project's specific aims are as follows: Aim 1 -- Devise computer-based methods for planning and guiding the bronchoscopic biopsy of peripheral lung nodules and mediastinal lymph nodes, thereby reducing the number of surgical biopsies and nodule resections and enabling less-invasive mediastinal lymph-node staging. Aim 2 -- Devise methods for MDCT-based analysis of diagnostically important pulmonary structures, thereby enabling more thorough and effective use of MDCT images. Aim 4 -- Perform human studies to compare the complete system to standard practice. Recent studies applying CT to population-based screening of at-risk smokers yield a large number of subjects with pulmonary nodules, as well as subjects with asymptomatic mediastinal lymph node enlargement. Most of these nodules and lymphadenomegaly will not be due to cancer. Further, bronchoscopic biopsy of small peripheral nodules and 1-2 cm lymph nodes have low yield, because of the considerable skill needed in traversing the 3D airway structure and the difficulty in making judgments on blind sites. Transcutaneous needle biopsy also has low yield for small nodules and has other potential complications. This leaves surgical removal, which has many drawbacks in terms of morbidity, cost, and the high rate of resecting benign structures. Finally, once lung cancer has been diagnosed, the impact of therapy and treatment remains largely unchanged over the last twenty years. Thus, methods are needed for: (1) early assessment of suspect lung pathologies; (2) planning and guidance of the biopsy procedure to improve yields and consequently improve early diagnosis and staging; and (3) accurate delivery of new therapies directly into the lung tumor nodule or involved lymph nodes. This competitive renewal proposes such methods. If successful, the project will have a major impact on the management of lung nodules detected by lung cancer screening or other MDCT applications to the lung, and on the appropriate staging of lung cancer. Finally, the methods should be generalizable to other organ systems, in particular to applications in neurology, urology, gynecology and gastroenterology. [unreadable] [unreadable]